The goal of this proposal is to develop a transformative, selective treatment for invasive bladder cancer through the use of our fiberoptic microneedle device (FMD). Specifically, we hypothesize that the FMD will enable the first minimally invasive treatment of stage 2-3 invasive bladder cancer through nanoparticle-enhanced photothermal therapy. The FMD will be used to selectively deliver novel photoabsorbing particles known as single walled nanohorns (SWNHs) in conjunction with laser energy to treat targeted tumors embedded within muscular and serosal layers of the bladder. The FMD will have the ability to both inject these chromophores directly into the tumor site and deliver accurate laser excitation to maximize tumor death and minimize systemic toxicity. Research will focused on analysis and modeling of the needle mechanics, fluid/particle dispersal, and light delivery. To realize the healing potential of this technology, the study will be conducted according to the following objectives: (1) Demonstrate the capability of the FMD for targeted penetration into selected bladder depths and nanoparticle and photothermal delivery in excised urinary bladders from normal rats, dogs, and pigs; (2) Integrate multifunctional optical and nanoparticle delivery capabilities of FMD within a clinical cystoscope and evaluate treatment using excised urinary bladders; (3) Evaluate the capability of the FMD for effective nanoparticle-enhanced photothermal therapy in rodent and canine models of transitional cell carcinoma. Completion of Objective 1 will allow critical characterization of the multifunctional capability of the FMD for mechanical insertion and optical/nanoparticle delivery necessary for development and utilization for the treatment of invasive bladder cancer. The result of Objective 2 will yield a novel instrument (FMD) which is integrated with a clinical cystoscope. Conclusion of Objective 3 will provide definitive answer to our hypothesis that the FMD can enable the first minimally invasive treatment of stage 2-3 invasive bladder cancer in rat and dog models. PUBLIC HEALTH RELEVANCE: The current method of treating invasive bladder cancer is surgical resection of the bladder and loss of urinary and sexual function. This research provides a positive step toward demonstrating the feasibility of treating aggressive invasive bladder cancer using a novel instrument in order to spare tissue function.